Koralnik I J, Du Pasquier R A, Letvin N L
Department of Neurology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
J Virol. 2001 Apr;75(7):3483-7. doi: 10.1128/JVI.75.7.3483-3487.2001.
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by a reactivation of the polyomavirus JC (JCV) within a setting of immunosuppression. The nature of the immune response that contains replication of this virus is unknown. We have explored JCV-specific cellular immune responses in patients with PML and control subjects. JCV antigen-stimulated peripheral blood mononuclear cells (PBMC) of four human immunodeficiency virus (HIV)-infected patients who were survivors of PML and one HIV-uninfected patient recently diagnosed with PML lysed autologous B-lymphoblastoid cell lines expressing either the JCV T regulatory protein or the VP1 major capsid protein. This lysis was mediated by CD8(+) T lymphocytes and was major histocompatibility complex class I restricted. These cells were therefore cytotoxic T lymphocytes (CTL). JCV-specific CTL could not be detected in PBMC of three HIV-infected PML patients who had progressive neurologic disease and an eventual fatal outcome. These data suggest that the JCV-specific cellular immune response may play a crucial role in the containment of PML. This finding may also prove useful as a favorable prognostic marker in the clinical management of these patients.
进行性多灶性白质脑病（PML）是一种中枢神经系统脱髓鞘疾病，由多瘤病毒JC（JCV）在免疫抑制环境下重新激活所致。抑制该病毒复制的免疫反应的本质尚不清楚。我们研究了PML患者和对照受试者中JCV特异性细胞免疫反应。4例感染人类免疫缺陷病毒（HIV）且为PML幸存者的患者以及1例最近诊断为PML的未感染HIV患者的JCV抗原刺激外周血单个核细胞（PBMC），裂解了表达JCV T调节蛋白或VP1主要衣壳蛋白的自体B淋巴母细胞系。这种裂解由CD8(+) T淋巴细胞介导，且受主要组织相容性复合体I类限制。因此，这些细胞为细胞毒性T淋巴细胞（CTL）。在3例患有进行性神经疾病并最终死亡的HIV感染PML患者的PBMC中未检测到JCV特异性CTL。这些数据表明，JCV特异性细胞免疫反应可能在PML的控制中起关键作用。这一发现也可能作为这些患者临床管理中的有利预后标志物而有用。
